Evidence suggests proton-pump inhibitor can lower risk of severe GI bleeding in the elderly on antiplatelet therapy
Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort studyLi L, Geraghty OC, Mehta Z, et al. - Lancet 2017; published online ahead of print
Guidelines on the secondary prevention of vascular events recommend the lifelong use of daily aspirin or other antiplatelet drugs, but they do not include any recommendations on proton-pump inhibitor (PPI) use, for the reduction of major bleeding risk in high-risk patients [1,2]. PPIs are not routinely prescribed in these patients, and the definitions of high risk in this case vary [3,4]. Relevant studies included mainly patients younger than 75 years, in primary prevention settings with a relatively short follow-up [5,6].
In this population-based cohort study, the age-specific risks, site, severity, outcomes, time course, and predictors of bleeding complications in secondary prevention of vascular events were determined, in order to estimate the potential effect of routine PPI use on reducing bleeding.
For this purpose, 3166 patients in the Oxford Vascular Study with a first acute TIA, ischemic stroke, or MI, who were treated with aspirin-based antiplatelet drugs in secondary prevention, but did not receive routine PPI treatment, were followed-up from 2002 until 2013. Patients on oral anticoagulants and patients with contraindications for antiplatelet therapy were not included in the study. Bleedings were considered to be disabling, if they resulted in a deterioration in functional independence (modified Rankin Scale increased to ≥3, or increased by ≥1 point if premorbid modified Rankin Scale ≥3) at hospital discharge without recovery by the next follow-up visit.
- The annual risk of major bleeding was higher in patients ≥75 at baseline compared with those <75, both at 3 years (HR: 2.73; 95% CI: 1.95–3.82; P<0.0001), as well as at 10 years (HR: 3.10; 95% CI: 2.27–4.24; P<0.0001). The increased 10-year risk was mainly driven by upper GI bleedings (HR: 4.13; 95% CI: 2.60–6.57; P<0.0001).
- Patients ≥75 had more severe bleedings than those <75 (ptrend<0.0001), and the outcome of non-fatal bleedings was worse at older ages.
- The proportion of survivors in whom an extracranial bleeding resulted in new or a sustained increase in disability increased with age (3% <75 years vs 25% ≥75 years; OR: 12.8; 95% CI: 4.5–36.6; P<0.0001), particularly after major upper GI bleedings (14% vs 53%; disability or death: 25% vs 62%).
- The long-term risk of disabling or fatal upper GI bleeding was ten times higher in patients ≥75 (HR: 10.26; 95% CI: 4.37–24.13; P<0.0001; AR: 9.15; 95% CI: 6.67–12.24 per 1000 patient-years), substantially outnumbering disabling or fatal intracerebral bleedings (n=18).
- The associations of major bleeding and major upper GI bleeding with age were independent of gender, history of vascular disease, vascular risk factors, and history of peptic ulcer.
- The absolute risks of major bleeding vs. ischemic events increased with age and REACH score. In patients <75 years, the ratio of major bleeds to ischemic events was 0.20 (95% CI: 0.14–0.27), and increased with age (75–84 years: 0.32; 95% CI: 0.23–0.43; ≥85 years: 0.46; 95% CI: 0.32–0.67), and the risk of major bleeds estimated to be attributable to antiplatelet treatment approached the risk of ischemic events estimated to have been prevented.
- The NNT with PPIs to prevent one major upper GI bleeding at 5 year follow-up decreased with increasing age: 80 for patients <65 years, 75 for patients aged 65–74 years, 23 for patients aged 75–84 years, and 21 for patients ≥ 85. The NNT with PPIs to prevent one disabling or fatal upper GI bleed at 5 year follow-up also decreased, from 338 for patients <65 years to 25 for patients ≥85.
In patients on secondary prevention for ischemic events, receiving antiplatelet therapy without routine PPI use, the long-term risk of bleeding at age 75 years or older is higher and more sustained compared with younger age groups, with particularly high risks of disabling or fatal upper GI bleeding. The estimated NNT for routine PPI use to prevent major upper GI bleed is low and co-prescription should be considered in future secondary prevention guidelines.